Neurotransmitter and neuromodulator imbalance in kisspeptin/GnRH regulation in rodent models of polycystic ovary syndrome and its implications for mental health disorders: A systematic review.
Level 5 - mechanism / opinion, no new human data
Systematic review of bench and animal (rodent) studies
PubMed 42140496 · doi:10.1016/j.bbr.2026.116262
What was done
Authors conducted a systematic review searching PubMed and Web of Science for rodent models of polycystic ovary syndrome (PCOS). They evaluated gene expression, protein expression, and neurotransmitter content related to gonadotropin-releasing hormone (GnRH) signaling across 52 included research articles.
What was found
No quantitative numerical values were reported in the abstract. In non-PCOS rodents, kisspeptinergic and noradrenergic signaling stimulated GnRH neurons, while serotonergic and GABAergic pathways showed receptor-dependent bidirectional effects. In PCOS rodent models, alterations depended on the induction method: postnatal androgenization reduced kisspeptinergic, monoaminergic, and GABAergic signaling to GnRH neurons; prenatal androgenization caused no change in kisspeptinergic signaling, with monoaminergic and GABAergic pathways requiring further study; and postnatal estrogenization caused decreased kisspeptinergic and GABAergic signaling alongside increased monoaminergic neurotransmission.
Why it matters
This review synthesizes preclinical evidence connecting reproductive neurocircuitry and mood-regulating neurotransmitter pathways in PCOS models. It highlights potential neurobiological mechanisms linking hyperandrogenic states to comorbid mental health disorders.
Limits
All data are from rodent models and cannot be directly extrapolated to human clinical PCOS. Findings varied considerably depending on the specific animal induction protocol used, some pathways remain unexamined in prenatal models, and the abstract provides no quantitative meta-analytic data.
Cited by
- partial Elevated androgens in PCOS disrupt brain dopamine and serotonin signaling.